This is a broad proposal to study metabolism in the ruminant under a variety of physiological conditions with particular reference to gluconeogenesis, ketogenesis, amino acid metabolism, N transport, mechanisms and hormonal control. The intact sheep is the basic animal model used but the dog sometimes is used for comparative studies between ruminant and simple-stomached animals. Emphasis is on the gut, liver, muscle, brain and kidneys by use of our techniques for continuous feeding, blood vessel catheterizations, blood flow, and tracer and mathematical techniques for measuring interconversions and unidirectional uptake and release of metabolites. Major metabolites to be measured are glucose, ketone bodies, acetate, propionate, lactate, glutamine-glutamine, alanine, urea cycle and branched-chain amino acids. The sheep has been an excellent animal model for study of metabolic dyscrosis. They absorb only little glucose, depend continuously on gluconeogenesis and are susceptible to hypoglycemia. Ketogenesis occurs in the digestive tract as well as liver. Nitrogen transport systems are essential for gluconeogenesis and N balance. Inter-organ cycles of glycine, glutamine, alanine, and urea-cycle and branched-chain amino acids are now known to occur.